Overlap and interdigitation of cortical and thalamic afferents to dorsocentral striatum in the rat

Dorsocentral striatum (DCS) is an associative region necessary for directed attention in rats. DCS is defined as the main region in which axons from ipsilateral medial agranular cortex (AGm) terminate within the striatum. In this double-labeling study, we placed a green axonal tracer in area AGm and a red one in an additional brain region. We examined the spatial relationship between terminals from area AGm and other portions of the cortical-basal ganglia-thalamic-cortical network involved in directed attention and its dysfunction, hemispatial neglect, in the rat. These include lateral agranular cortex (AGl), posterior parietal cortex (PPC), ventrolateral orbital cortex (VLO), and secondary visual cortex (Oc2M). One important finding is the presence of a dense focus of labeled axons within DCS after injections in cortical area PPC or Oc2M. In these foci, axons from PPC or Oc2M extensively overlap and interdigitate with axons from cortical area AGm. Additionally, retrograde labeling of striatal neurons, along with double anterograde labeling, suggests that axons from cortical area AGm and AGl cross and possibly make contact with the dendritic processes of single medium spiny neurons. Axons from thalamic nucleus LP were observed to form a dense band dorsal to DCS which is similar to that seen following PPC injections, and a significant number of LP axons were also observed within DCS. Projections from thalamic nucleus VL are present in the dense dorsolateral AGm band that abuts the external capsule, are densest in the dorsolateral striatum, and were not observed in DCS. These results extend previous findings that DCS receives input from diverse cortical areas and thalamic nuclei which are themselves interconnected.     

The associative striatum: cortical and thalamic projections to the dorsocentral striatum in rats

Corticostriatal projections to the dorsocentral striatum (DCS) were investigated using retrograde fluorescent axonal tracing. The DCS is of interest because of its role in directed attention and recovery from multimodal hemispatial neglect following cortical lesions of medial agranular cortex (AGm), an association area that is its major source of cortical input. A key finding was that the multimodal posterior parietal cortex (PPC) also contributes substantial input to DCS. This is significant because PPC and AGm are linked by corticocortical connections and are both critical components of the circuitry involved in spatial processing and directed attention. Other cortical areas providing input to DCS include visual association areas, lateral agranular cortex and orbital cortex. These areas also have reciprocal connections with AGm and PPC. Less consistent labeling was seen in somatic sensorimotor areas FL, HL and Par 1. Thalamic afferents to DCS are prominent from the intralaminar, ventrolateral, mediodorsal, ventromedial, laterodorsal (LD) and lateral posterior (LP) nuclei. Collectively, these nuclei constitute the sources of thalamic input to cortical areas AGm and PPC. Nuclei LD and LP are only labeled with injections in dorsal DCS, the site of major input from PPC, and PPC receives its thalamic input from LD and LP. We conclude that DCS receives inputs from cortical and thalamic areas that are themselves linked by corticocortical and thalamocortical connections. These findings support the hypothesis that DCS is a key component of an associative network of cortical, striatal and thalamic regions involved in multimodal processing and directed attention.     

Topographic organization in the corticocortical connections of medial agranular cortex in rats

Medial agranular cortex (AGm) is a narrow, longitudinally oriented region known to have extensive corticortical connections. The rostral and caudal portions of AGm exhibit functional differences that may involve these connections. Therefore we have examined the rostrocaudal organization of the afferent cortical connections of AGm by using fluorescent tracers, to determine whether there are significant differences between rostral and caudal AGm. Mediolateral patterns have also been examined in order to compare the pattern of corticocortical connections of AGm to those of the laterally adjacent lateral agranular cortex (AGl) and medially adjacent anterior cingulate area (AC). In the rostrocaudal domain, there are notable patterns in the connections of AGm with somatic sensorimotor, visual, and retrosplenial cortex. Rostral AGm receives extensive afferents from the caudal part of somatic sensorimotor area Par I, whereas caudal AGm receives input largely from the hindlimb cortex (area HL). Middle portions of AGm show an intermediate condition, indicating a continuously changing pattern rather than the presence of sharp border zones. The whole of the second somatic sensorimotor area Par II projects to rostral AGm, whereas caudal AGm receives input only from the caudal portion of Par II. Visual cortex projections to AGm originate in areas Oc1, Oc2L and Oc2M. Connections of rostral AGm with visual cortex are noticeably less dense than those of mid and caudal AGm, and are focused in area Oc2L. The granular visual area Oc1 projects almost exclusively to mid and caudal AGm. Retrosplenial cortex has more extensive connections with caudal AGm than with rostral AGm, and the agranular and granular retrosplenial subregions are both involved. Other cortical connections of AGm show little or no apparent rostrocaudal topography. These include afferents from orbital, perirhinal, and entorhinal cortex, all of which are bilateral in origin. In the mediolateral dimension, AGm has more extensive corticocortical connections than either AGl or AC. Of these three neighboring areas, only AGm has connections with the somatic sensorimotor, visual, retrosplenial and orbital cortices. In keeping with its role as primary motor cortex, AGl is predominantly connected with area Par I of somatic sensorimotor cortex, specifically rostral Par I. AGl receives no input from visual or retrosplenial cortex. Anterior cingulate cortex has connections with visual area Oc2 and with retrosplenial cortex, but none with somatic sensorimotor cortex. Orbital cortex projections are sparse to AGl and do not appear to involve AC.(ABSTRACT TRUNCATED AT 400 WORDS)     

Efferent connections of the rostral portion of medial agranular cortex in rats

This study of the rostral part of medial agranular cortex (AGm) was undertaken with two principal aims in mind. First, to delineate the efferent connections of AGm and compare these with the pattern of afferents defined by us in a previous study. Second, to provide a firmer basis for anatomical and functional comparisons with cortical regions in monkeys. Autoradiographic, horseradish peroxidase, and fiber degeneration techniques were used. Rostral AGm has a variety of corticocortical connections--with lateral agranular motor cortex (AGl); visual, auditory, and somatic sensory regions; and limbic/paralimbic areas including orbital, insular, perirhinal, entorhinal, retrosplenial and presubicular fields. The projections to orbital, perirhinal and entorhinal cortices are bilateral. Thalamic projections of rostral AGm are concentrated in the ventral lateral, central lateral, paracentral, mediodorsal and ventromedial nuclei. Moderate terminal fields are consistently seen in the reticular, anteromedial, central medial, gelatinosus, parafascicular, and posterior nuclei. More caudal projections reach the central gray, superior colliculus and pontine gray. The efferents of the adjacent AGl were also examined. Although many of these overlapped those of rostral AGm, there were no efferents to visual or auditory cortex and limbic/paralimbic projections were reduced. Thalamic projections were more focused in the ventral lateral and posterior nuclei and there were no terminal fields in the central gray or superior colliculus. Based on its afferent and efferent connections, role in contralateral neglect, and the results of microstimulation studies, rostral AGm can be viewed as a multimodal association area with strong ties to the motor system. On these structural and functional grounds, rostral AGm bears certain striking resemblances to the frontal eye field, supplementary motor, and arcuate premotor areas of monkey cortex.     

Unilateral destruction of the dorsocentral striatum in rats produces neglect but not extinction to bilateral simultaneous stimulation

A number of previous studies have indicated that lesions of the medial agranular cortex (AGm) in rats induce multimodal neglect and extinction to bilateral simultaneous stimulation (extinction), the two major symptoms of the neglect syndrome in humans. A recent study demonstrated that lesions of dorsocentral striatum (DCS), the site of AGm projections to the striatum, produce multimodal neglect qualitatively similar to that found with AGm lesions. In the present study, the behavioral effects of unilateral DCS lesions were examined in more detail for the major manifestations of neglect: hemineglect, extinction, and allesthesia/allokinesia. Subjects were tested for extinction to bilateral simultaneous stimulation of the forepaws three times a week for 3 weeks. Neglect testing occurred twice weekly and the subjects were tested for the presence of neglect by rating the magnitude of orientation to visual, tactile, and auditory stimulation. The results indicated that DCS operates, while demonstrating severe neglect, failed to demonstrate extinction or allesthesia/allokinesia. These findings suggest that the neural mechanisms that underlie neglect and extinction are dissociable in this system. A better understanding of the neural mechanisms that underlie extinction is particularly important because humans that have recovered from neglect often continue to demonstrate the debilitating symptoms of extinction.     

Effects of light deprivation on recovery from neglect and extinction induced by unilateral lesions of the medial agranular cortex and dorsocentral striatum

A number of previous studies have indicated that an environmental manipulation, 48 h of light deprivation (LD), produces virtually complete and permanent behavioral recovery of function from neglect induced by medial agranular cortex (AGm) lesions. LD-induced behavioral recovery from neglect is correlated with physiological changes in the dorsolateral striatum, an area that contains the projection zone of AGm efferents in the dorsocentral striatum (DCS). In this study, the behavioral effects of 48 h of LD on subjects with either unilateral DCS, AGm, or combined AGm/DCS lesions were investigated to examine whether the integrity of the DCS is crucial for behavioral recovery from neglect and whether LD will have a therapeutic effect on extinction deficits. Subjects were tested for extinction to bilateral simultaneous stimulation of the forepaws, and visual, auditory and tactile neglect. Forty-eight hours of LD failed to produce behavioral recovery from neglect in rats with DCS lesions, or a therapeutic affect on extinction deficits in any of the groups. The results of this study further support the crucial role of the DCS in recovery from neglect induced by AGm lesions and suggests that the DCS may be the crucial site for the mechanisms leading to LD-induced recovery. Further, the ineffectiveness of LD on extinction suggests that components of the neglect syndrome are dissociable and may require different therapeutic interventions.     

Quantitative analyses of thalamic and cortical origins of neurons projecting to the rostral and caudal forelimb motor areas in the cerebral cortex of rats

On the basis of studies using intracortical microstimulation, the existence of rostrocaudally separate two forelimb representation areas has been inferred in the motor cortex of rats. They are termed caudal and rostral forelimb areas (CFA and RFA). In this study, it was confirmed first that RFA and CFA are located in cytoarchitectonically distinct areas (medial and lateral parts of agranular cortex (AGm and AGl), respectively). In the second part of this study, the distribution of thalamic and cortical neurons projecting to RFA and CFA was quantitatively compared by injections of small and relatively constant amounts of retrograde fluorescent dyes (diamidino yellow and fast blue) into these areas. It was observed that (1) main inputs to RFA originated from AGl, namely CFA (2) CFA received dominant inputs from AGm including RFA and caudally adjacent granular cortex and (3) wider cortical areas and larger number of neurons projected to CFA than to RFA. As for the thalamocortical projections, both RFA and CFA received inputs from various thalamic nuclei, such as VL, VM, Po, PC, PF, CL, but cells projecting to RFA and CFA were differentially located in each nucleus. It was found that labeled cell number and/or density in VM, PC, CL, CM and MD after RFA injections were significantly larger than those after CFA injections. On the other hand, labeled cell number and/or density in VPL and VL were significantly higher after CFA injections than after RFA injections. In comparison with findings in primates, the results suggest that the cortical motor areas of rats may be specialized for different aspects of motor control.     

Origins and collateralization of corticospinal, corticopontine, corticorubral and corticostriatal tracts: a multiple retrograde fluorescent tracing study.

Cerebral cells of origin for the corticospinal (CST), corticopontine (CP), corticorubral (CR) and corticostriatal (CS) fibers in the rat were identified following the simultaneous retrograde transport of propidium iodide (PI), fast blue (FB), fluorogold (FG) and diamidino yellow (DY). PI was injected into the contralateral C4 spinal cord segment while FB, FG and DY were injected into the ipsilateral medial pontine nuclei, red nucleus and striatum, respectively. Labeled pyramidal neurons projecting corticospinal axons were contralateral to injection in lamina V and ranged in size from small to large. These CST neurons occupied two distinct cortical areas. The cortical neurons of origin for the corticopontine, corticorubral and corticostriatal fibers were ipsilateral to injections. Labeled neurons were localized in cortical lamina V for the corticopontine and corticorubral fibers while corticostriate neurons were located in laminae III, V and VI. The CP, CR and CS labeled cells occupied one large cortical area which topographically included parts of the medial (AGm) and lateral (AGl) agranular cortices and the primary (SI) somatosensory cortex. Considerable overlapping of the cortical neurons of origin for the four motor fiber systems was apparent. More than 98% of the labeled cells were single labeled while less than 2% were double labeled. No triple or quadruple labeled neurons were observed. Hence, morphological evidence is presented that cortical motor neurons project mainly individual, rather than collateral, axons to each of the four motor associated nuclei investigated in this study. However, only a few cortical neurons projected axons simultaneously to a maximum of two nuclei involved in the motor pathways.     

Relationship between the corticostriatal terminals from areas 9 and 46, and those from area 8A, dorsal and rostral premotor cortex and area 24c: an anatomical substrate for cognition to action

Our previous data indicate that there are specific features of the corticostriatal pathways from the prefrontal cortex. First, corticostriatal pathways are composed of focal, circumscribed projections and of diffuse, widespread projections. Second, there is some convergence between terminal fields from different functional regions of the prefrontal cortex. Third, anterior cingulate projections from area 24b occupy a large region of the rostral striatum. The goal of this study was to determine whether these features are also common to the corticostriatal projections from area 8A (including the frontal eye field; FEF), the supplementary eye field (SEF), dorsal and rostral premotor cortex (PMdr) and area 24c. Using a new approach of three-dimensional reconstruction of the corticostriatal pathways, along with dual cortical tracer injections, we mapped the corticostriatal terminal fields from areas 9 and 46, 8A-FEF, SEF, PMdr and 24b and c. In addition, we placed injections of retrogradely transported tracers into key striatal regions. The results demonstrated that: (i) a diffuse projection system is a common feature of the corticostriatal projections from different frontal regions; (ii) key striatal regions receive convergent projections from areas 9 and 46 and from areas 8A-FEF, SEF, PMdr and 24c, suggesting a potential pivotal role of these striatal regions in integrating cortical information; (iii) projections from area 24c, like those from area 24b, terminate widely throughout the striatum, interfacing with terminals from several frontal areas. These features of the corticostriatal frontal pathways suggest a potential integrative striatal network for learning.     

Topographic organization of the striatal and thalamic connections of rat medial agranular cortex.

The rostral and caudal portions of rat medial agranular cortex (AGm) play different functional roles. To refine the anatomical framework for understanding these differences, axonal tracers were used to map the topography of the connections of AGm with the striatum and thalamus. The striatal projections follow mediolateral and rostrocaudal gradients that correspond to the locations of the neurons of origin within AGm. Projections from rostral AGm are widespread and dense rostrally, then coalesce into a circumscribed dorsocentral region at the level of the pre-commissural septal nuclei. Projections from mid and caudal AGm are less widespread and less dense, and are focused more caudally. Striatal projections from the adjacent anterior cingulate and lateral agranular areas overlap those of AGm but are concentrated more medially and laterally, respectively. Thalamic connections of AGm are organized so that more caudal portions of AGm have connections with progressively more lateral and caudal regions of the thalamus, and the full extent of AGm is connected with the ventrolateral (VL) nucleus. Rostral AGm is interconnected with the lateral portion of the mediodorsal nucleus (MD1), VL, and the central lateral (CL), paracentral (PC), central medial, rhomboid and ventromedial nuclei. Caudal AGm has robust connections with VL, the posterior, lateral posterior and lateral dorsal nuclei, but little or none with MD1, CL/PC and VM. These differences in the subcortical connections of rostral and caudal AGm parallel their known differences in corticocortical connections, and represent another basis for experimental explorations of the functional roles of these cortical territories.     

Patterns of sensory intermodality relationships in the cerebral cortex of the rat.

Patterns of connections underlying cross-modality integration were studied by injecting distinguishable, retrograde tracers (Fluoro-Gold and diamidino yellow) in pairwise manner into different sensory representations (visual, somatosensory, and auditory) in the cerebral cortex of the rat. In agreement with previous single tracer studies, our results indicate that the central core of sensory areas receives projections mainly from a set of association areas located in a ringlike fashion along the margin of the cortical mantle. The visual cortex received projections from areas 48/49, area 29d, posterior agranular medial cortex (AGm), area 11, area 13, and area 35. All these areas were also connected to the auditory cortex with the exception of areas 29d and AGm. However, lateral to area 29d and posterior AGm, a band of neurons projecting to the auditory cortex was present. Somatosensory cortex was connected mainly with the more anterior aspect of the hemisphere, which included primary motor area, area 11, and area 13. The patterns of intermodality relationships revealed in the present study were of two main categories. In the anterior and lateral areas, an intermingling of cells projecting to different sensory modalities was observed. In contrast, in areas located along the medial aspect of the hemisphere, cells connected to different sensory modality representations tended to be segregated from each other. Postsubicular cortex (areas 48/49) contained both intermingled and segregated groups of cells. The incidence of clearly identified double-labeled cells concurrently projecting to two different sensory representations was extremely rare. These patterns may form a substrate for different levels of cross-modal sensory integration in the rat cortex.     

Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat.

The anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to examine the topographical organization of the projections to the striatum arising from the various cytoarchitectonic subdivisions of the prefrontal cortex in the rat. The relationship of the prefrontal cortical fibres with the compartmental organization of the ventral striatum was assessed by combining PHA-L tracing and enkephalin-immunohistochemistry. The prefrontal cortex projects bilaterally with an ipsilateral predominance to the striatum, sparing only the lateral part of the caudate-putamen complex. Each of the cytoarchitectonic subfields of the prefrontal cortex has a longitudinally oriented striatal terminal field that overlaps slightly with those of adjacent prefrontal areas. The projections of the medial subdivision of the prefrontal cortex distribute to rostral and medial parts of the striatum, whereas the lateral prefrontal subdivision projects to more caudal and lateral striatal areas. The terminal fields of the orbital prefrontal areas involve midventral and ventromedial parts of the caudate-putamen complex. The projection of the ventral orbital area overlaps with that of the prelimbic area in the ventromedial part of the caudate-putamen. In the "shell" region of the nucleus accumbens, fibres arising from the prelimbic area concentrate in areas of high cell density that are weakly enkephalin-immunoreactive, whereas fibres from the infralimbic area avoid such areas. Rostrolaterally in the "core" region of the nucleus accumbens, fibres from deep layer V and layer VI of the dorsal part of the prelimbic area avoid the enkephalin-positive areas surrounding the anterior commissure and distribute in an inhomogeneous way over the intervening moderately enkephalin-immunoreactive compartment. The other prefrontal afferents show only a preference for, but are not restricted to, the latter compartment. In the border region between the nucleus accumbens and the ventromedial part of the caudate-putamen complex, patches of strong enkephalin immunoreactivity receive prefrontal cortical input from deep layer V and layer VI, whereas fibres from more superficial cortical layers project to the surrounding matrix. Individual cytoarchitectonic subfields of the prefrontal cortex thus have circumscribed terminal domains in the striatum. In combination with data on the organization of the midline and intralaminar thalamostriatal and thalamoprefrontal projections, the present results establish that the projections of the prefrontal cortical subfields converge in the striatum with those of their midline and intralaminar afferent nuclei. The present findings further demonstrate that the relationship of the prefrontal corticostriatal fibres with the neurochemical compartments of the ventral striatum can be influenced by both the areal and the laminar origin of the cortical afferents, depending on the particular ventral striatal region under consideration.     

Architecture and organization of mouse posterior parietal cortex relative to extrastriate areas

The posterior parietal cortex (PPC) is a multifaceted region of cortex, contributing to several cognitive processes, including sensorimotor integration and spatial navigation. Although recent years have seen a considerable rise in the use of rodents, particularly mice, to investigate PPC and related networks, a coherent anatomical definition of PPC in the mouse is still lacking. To address this, we delineated the mouse PPC, using cyto‐ and chemoarchitectural markers from Nissl‐, parvalbumin‐and muscarinic acetylcholine receptor M2‐staining. Additionally, we performed bilateral triple anterograde tracer injections in primary visual cortex (V1) and prepared flattened tangential sections from one hemisphere and coronal sections from the other, allowing us to co‐register the cytoarchitectural features of PPC with V1 projections. This revealed that extrastriate area A was largely contained within lateral PPC, that medial PPC overlapped with the anterior portion of area AM, and that anterior RL overlapped partially with area PtP. Furthermore, triple anterograde tracer injections in PPC showed strong projections to associative thalamic nuclei as well as higher visual areas, orbitofrontal, cingulate and secondary motor cortices. Retrograde circuit mapping with rabies virus further showed that all cortical connections were reciprocal. These combined approaches provide a coherent definition of mouse PPC that incorporates laminar architecture, extrastriate projections, thalamic, and cortico–cortical connections.     

Infusion of apomorphine into the dorsocentral striatum produces acute drug-induced recovery from neglect produced by unilateral medial agranular cortex lesions in rats

Previous studies have shown that systemic administration of apomorphine is effective in producing acute drug-induced recovery from neglect induced by unilateral medial agranular cortex (AGm) lesions. More recent studies have demonstrated that recovery from neglect may be due to plastic changes occurring in the dorsal central striatum (DCS). Further, lesions of the DCS produce neglect that does not respond to systemic administration of apomorphine, suggesting that this area may be crucial for the therapeutic effects of apomorphine. In the present study, the behavioral effects of apomorphine infused into the DCS of animals with AGm lesion-induced neglect were examined to determine whether the DCS is a site of drug action. An infusion of 0.375 micro g of apomorphine into the DCS, but not a lateral striatal control area, was effective in producing acute recovery from neglect. The results of this study support the crucial role of the DCS in recovery from neglect induced by unilateral AGm lesions and suggest that the DCS may be an important site of action for the therapeutic effects of apomorphine. Because dopamine agonist therapy has been shown to be effective in humans with neglect, the results of the current study may represent an important step in the development of future pharmacotherapies.     

Postsynaptic potentials evoked in spiny neostriatal projection neurons by stimulation of ipsilateral and contralateral neocortex

Postsynaptic potentials were evoked in neostriatal neurons by stimulation of the ipsilateral and contralateral medial agranular frontal cortical field (AGm) in the rat. This cortical region is known to project bilaterally to the dorsal lateral head of the caudate-putamen of rats. Ipsilateral stimulation of AGm should excite all types of corticostriatal neurons projecting to neostriatal neurons in the corresponding area in neostriatum, while stimulation of the same cortical area on the side contralateral to the recording should evoke synaptic potentials from a more restricted subpopulation of crossed corticostriatal neurons. Neostriatal neuronal responses were recorded intracellularly and spiny projection neurons identified by intracellular staining with horseradish peroxidase. The initial EPSP response to contralateral stimulation was similar to that evoked from the ipsilateral side, except for the absence of a relatively small short latency component responsible for the earliest part of the response to ipsilateral cortical stimulation. Comparison with previous findings indicated that this earliest EPSP component was due to activation of fast-conducting descending cortical efferents with collateral projections exclusively to the ipsilateral neostriatum. Stimulation of contralateral neostriatum evoked responses identical to those obtained using stimulation of contralateral neocortex. Analyses of these responses indicated that both EPSPs arise from activation of the same population of fibers. Stimulation of the contralateral internal capsule just caudal to neostriatum was not effective in evoking the EPSP. Chronic hemidecortication did not change the shape of the EPSP evoked from the intact contralateral side, but reduced its amplitude by approximately one half. These observations indicate that contralaterally projecting corticostriatal neurons in the rat project bilaterally in neostriatum, have axonal branches to the contralateral cerebral cortex as well as neostriatum, and converge onto neostriatal neurons that also receive input from the corresponding cortical region on the ipsilateral side.     

Primate striatonigral projections: A comparison of the sensorimotor-related striatum and the ventral striatum

The striatum receives topographic cortical inputs with the limbic lobe terminating in the ventral striatum and sensorimotor cortical regions terminating in the dorsolateral striatum. The organization of striatonigral projections originating from these different striatal territories was examined in primate by using several anterograde tracers. The ventral striatum innervates a large area of the substantia nigra, including the medial pars reticulata and much of the pars compacta. Moreover, projections from separate areas of the ventral striatum overlap considerably in the substantia nigra. No mediolateral or rostrocaudal topographic order is apparent, and the area of the substantia nigra associated with the ventral striatum is extensive. In contrast, the sensorimotor-related striatum innervates a limited region of the ventrolateral substantia nigra. Similar to ventral striatonigral projections, projections originating from different areas of the sensorimotor-related striatum send converging inputs to the substantia nigra. Sensorimotor-related striatonigral projections avoid the region of the dopaminergic neurons in the dorsal pars compacta. Striatonigral projections from the sensorimotor-related and ventral striatum do not overlap in the substantia nigra. Examination of the outputs of discrete striatal loci indicates that the organization of striatonigral projections is more related to corticostriatal inputs than to a simple rostrocaudal, dorsoventral, or mediolateral tpography of the striatum. Striatal projections that originate from different striatal territories are distinct and nonoverlapping, thus supporting the concept of segregated striatonigral circuits. However, areas of the striatum that receive common cortical inputs send converging inputs to the substantia nigra. This suggests that the substantia nigra is also an important link for integrating information between functionally related (sub)circuits. © 1994 Wiley-Liss, Inc.     

Visceral cortex: integration of the mucosal senses with limbic information in the rat agranular insular cortex

The organization of the subcortical and cortical connections of the rat agranular insular cortex was examined. Retrogradely transported dyes were used to map the agranular insular cortex efferents to brainstem visceral nuclei (the nucleus of the solitary tract and the parabrachial nucleus), to gustatory-visceral and limbic thalamic nuclei (medial ventrobasal and mediodorsal thalamus, respectively), and to association cortex (medial prefrontal and contralateral agranular insular cortex). The results revealed that a specific area within the ipsilateral agranular insular cortex projected to all of the subcortical and cortical areas listed above. This area of overlap in the agranular insular cortex stretched from the level of the genu of the corpus callosum rostrally to the crossing of the anterior commissure caudally. Anterograde projections from the medial ventrobasal and mediodorsal thalamus and from the olfactory bulb to the agranular insular cortex were mapped with wheat germ agglutinin conjugated to horseradish peroxidase. The terminal cortical projections from these areas were generally separate, except in an area where they overlap immediately medial to the rhinal fissure in the agranular insular cortex. This overlap area matched the area in the agranular insular cortex where there was an overlap of cortical efferent cells projecting to the brainstem, thalamus, and association cortex, as revealed in the retrograde tracing studies. We refer to this region of convergence in the agranular insular cortex as the visceral cortex, and suggest its involvement in the efficient integration of specific visceral sensory stimuli with correlated limbic or motivational consequences. The visceral cortex may help regulate the organism's visceral response to stress.     

Cells of origin and terminal distribution of corticostriatal fibers arising in the sensory-motor cortex of monkeys.

The cells of origin of the corticostriatal projection have been identified in squirrel monkeys by the use of the retrograde horseradish peroxidase method. In the subfields of the somatic sensory, motor, parietal and frontal areas of the cortex, cells projecting to the ipsilateral striatum are relatively sparsely distributed and form a group of small- to medium-sized pyramidal cells with an average somal diameter from area to area of 14-16 mum. Such cells are found only in layer V of the cortex (mainly in the more superficial parts of the layer). Since they are consistently smaller than the pyramidal cells of layer V that project to the brainstem and spinal cord and since they lie outside layer VI which gives rise to corticothalamic axons, the corticostriatal axons are unlikely to be collaterals of axons projecting to other sites. The cells of origin of the crossed corticostriatal projection are also found in layer V and are pyramidal cells with somal diameters in the same range as above. They are found only in areas 4, 8, and 6. Studies with the anterograde, autoradiographic method in rhesus, cynomologous and squirrel monkeys, indicate that the somatic sensory areas project to most of the antero-posterior extent of the ipsilateral putamen. Subareas 3a, 3b, 1 and 2 of the somatic sensory cortex project to the same region and the projection overlaps similarly extensive projections from the motor and certain other areas of the cortex. However, in each case the pattern of terminal labeling is in the form of interrupted clusters, strips and bands. A single small injection of the cortex is associated with only one or two such clusters of terminal labeling. This seems to imply that individual corticostriatal fibers end in a very restricted manner and that the terminal ramifications of fibers from one cortical area may alternate in the putamen with those arising in other areas.     

Nuclear terminations of corticoreticular fiber systems in rats

Corticoreticular fiber systems were examined in adult albino and hooded rats using anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and anterograde degeneration. WGA-HRP injections were made stereotactically into the medial prefrontal cortex, the medial agranular cortex, the anterior cingulate cortex, the face motor cortex, the forelimb motor cortex, the trunk-hindlimb motor cortex, the face somatosensory cortex, the primary auditory cortex, the secondary visual cortex and the primary visual cortex. With exception of the cingulate cortex (which is relatively inaccessible to lesioning methods) and the primary visual cortex, electrocautery lesions were made into these same cortical areas. The precise locations of cortical injection/lesion sites were corroborated on the basis of cortical cytoarchitectonic criteria, patterns of retrograde and anterograde thalamic labeling, and patterns of anterograde labeling in non-reticular brainstem nuclei such as the red nucleus, trigeminal nuclei and dorsal column nuclei. The heaviest corticoreticular projections arise from the medial agranular cortex. The medial prefrontal cortex also gives rise to consistently strong corticoreticular projections. The anterior cingulate cortex sends robust corticoreticular projections to the upper brainstem but relatively weak projections to the lower brainstem. With respect to the primary motor cortex, the face area gives rise to the densest corticoreticular projections, rivaling those emanating from the medial agranular cortex. The trunk-hindlimb area gives rise to substantial corticoreticular projections, but those originating from the forelimb area are modest and directed chiefly to midbrain and medullary levels. The face area of the somatosensory cortex gives rise to rather weak corticoreticular projections, while those arising from the primary auditory cortex are fewer still. Descending projections from the secondary visual cortex are sparse, with labeled terminals occurring in a few pontine and medullary reticular nuclei. Only one brainstem reticular nucleus (nucleus cuneiformis) was found to receive projections from the primary visual cortex, and this input was extremely sparse. Corticoreticular projections to the upper brainstem terminate predominantly ipsilateral to the cortical injection site, whereas medullary corticoreticular projections distribute bilaterally. Corticoreticular fibers from the medial agranular, face motor and trunk-hindlimb motor cortex terminate heavily in somatomotor brainstem reticular nuclei such as the pontis oralis, the pontis caudalis and the gigantocellularis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Synaptic convergence of motor and somatosensory cortical afferents onto GABAergic interneurons in the rat striatum

Cortical afferents to the basal ganglia, and in particular the corticostriatal projections, are critical in the expression of basal ganglia function in health and disease. The corticostriatal projections are topographically organized but also partially overlap and interdigitate. To determine whether projections from distinct cortical areas converge at the level of single interneurons in the striatum, double anterograde labeling from the primary motor (M1) and primary somatosensory (S1) cortices in the rat, was combined with immunolabeling for parvalbumin (PV), to identify one population of striatal GABAergic interneurons. Cortical afferents from M1 and S1 gave rise to distinct, but partially overlapping, arbors of varicose axons in the striatum. PV-positive neurons were often apposed by cortical terminals and, in many instances, apposed by terminals from both cortical areas. Frequently, individual cortical axons formed multiple varicosities apposed to the same PV-positive neuron. Electron microscopy confirmed that the cortical terminals formed asymmetric synapses with the dendrites and perikarya of PV-positive neurons as well as unlabelled dendritic spines. Correlated light and electron microscopy revealed that individual PV-positive neurons received synaptic input from axon terminals derived from both motor and somatosensory cortices. These results demonstrate that, within areas of overlap of functionally distinct projections, there is synaptic convergence at the single cell level. Sensorimotor integration in the basal ganglia is thus likely to be mediated, at least in part, by striatal GABAergic interneurons. Furthermore, our findings suggest that the pattern of innervation of GABAergic interneurons by cortical afferents is different from the cortical innervation of spiny projection neurons.